CN108409747B - Synthetic method of 2-aminoquinoline dihydrofuran compound - Google Patents
Synthetic method of 2-aminoquinoline dihydrofuran compound Download PDFInfo
- Publication number
- CN108409747B CN108409747B CN201810171226.6A CN201810171226A CN108409747B CN 108409747 B CN108409747 B CN 108409747B CN 201810171226 A CN201810171226 A CN 201810171226A CN 108409747 B CN108409747 B CN 108409747B
- Authority
- CN
- China
- Prior art keywords
- mmol
- aminoquinoline
- aminophenyl
- reaction
- ethyl acetate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
Abstract
The invention discloses a synthetic method of a 2-aminoquinoline dihydrofuran compound. The synthesis method comprises the following steps: dissolving o-aminophenyl homopropargyl alcohol, a palladium salt catalyst, a ligand and an oxidant in an organic solvent in a reactor, adding isonitrile, stirring for reaction at 80-100 ℃, and separating and purifying reaction liquid to obtain the 2-aminoquinoline dihydrofuran compound. The method develops a synthetic method for constructing the 2-aminoquinoline dihydrofuran compound with unique performance through the serial cyclization reaction of the o-aminophenyl homopropargyl alcohol and the isonitrile, wherein the o-aminophenyl homopropargyl alcohol serving as a basic raw material can be synthesized by cheap o-iodoaniline and 3-butyn-1-ol, and the method has the characteristics of simple and easily obtained raw materials, cheap operation, mild conditions, high atom economy and wide substrate applicability.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of a 2-aminoquinoline dihydrofuran compound.
Background
The quinofuran compounds are widely present in natural and non-natural compounds, and have unique biological and pharmaceutical activities due to the fact that the quinofuran compounds simultaneously contain two skeletons of quinoline and furan, and therefore, the quinofuran compounds are widely applied to synthesis research of novel functional molecules and medicines. Such products are currently obtained, through literature studies, mainly by intramolecular or intermolecular tandem cyclization reactions (s.j.ghaarpure, y.g.shelkej.org.chem.2017,82,2067; w.j.yang, h.j.ren, org.lett.2013,15,1282; r.halim, b.l.flynn, org.lett.2008,10,1967; r.halim, b.l.flynn, j.org.chem.2013,78,4708; c.zhu, s.m.ma, angew.chem.int.ed.2014,53,13532; h.r.park, e.k.yum, bull.korea chem.soc.2016,37,958). Generally, although the synthesis methods reported at present are greatly improved in terms of synthesis methods, some reactions require quinoline to be prepared in advance, or explosive azide compounds are used as raw materials, so that the reaction operation is complicated. In consideration of the great role of the furan quinoline skeleton in the fields of natural product research and medical and biological application, the development of more convenient and efficient synthetic methods is necessary.
One-step synthesis of polycyclic skeleton compounds is always a difficult problem in organic synthesis chemistry and drug research, and is also always a research hotspot field. In recent years, many complex molecules have been obtained from simple and readily available starting materials by taking advantage of the high efficiency and economy of the tandem reaction (l. -q. lu, w. -j. xiao, Accounts of Chemical Research,2012,45, 1278). The realization of the tandem reaction firstly needs to select a proper substrate and realize the one-step construction of the polycyclic framework through condition screening. In the reaction process, separation and purification are not needed, so that the reaction efficiency can be improved, and the reaction system has a certain industrial development prospect.
Therefore, the development of the high-efficiency synthesis of the quinolinofuran compound by using the tandem cyclization reaction under mild conditions has very important significance.
Disclosure of Invention
The invention aims to provide a synthetic method of a 2-aminoquinoline dihydrofuran compound aiming at the defects of the prior art. The method uses simple and easily obtained homopropargyl alcohol and isonitrile as raw materials, common palladium salt as a catalyst and mild copper salt as an oxidant to construct the polysubstituted quinoline dihydrofuran compound, has the characteristics of high atom economy, mild conditions, cheap and safe operation, wide substrate applicability and the like, and has good application prospect in actual production and research.
The purpose of the invention is realized by the following technical scheme.
A synthetic method of 2-aminoquinoline dihydrofuran compounds comprises the following steps:
dissolving o-aminophenyl homopropargyl alcohol, a palladium salt catalyst, a ligand and an oxidant in an organic solvent in a reactor, adding isonitrile, stirring for reaction at 80-100 ℃, and separating and purifying reaction liquid to obtain the 2-aminoquinoline dihydrofuran compound.
Further, the chemical reaction equation of the synthesis process is as follows:
in the formula, R1Is a substituent on the benzene ring, R1One or more selected from the group consisting of 4-methyl, 4-bromo, 4-methoxy, 4-ester, 5-chloro, 5-methyl, 5-trifluoromethyl, 5-bromo, 6-fluoro, 3, 5-dimethyl, 3, 5-dichloro, 4, 6-dimethyl and 4, 6-dichloro, wherein the numbers preceding the groups represent the positions of the groups on the phenyl ring;
R2selected from the group consisting of hydrogen and ethyl;
R3selected from the group consisting of tert-butyl, cyclohexyl, adamantyl, and 1,1,4, 4-tetramethylbutyl.
Further, the palladium salt catalyst is palladium tetratriphenylphosphine, and the molar ratio of the added amount of the palladium salt catalyst to the o-aminophenyl homopropargyl alcohol is 0.05-0.1: 1.
Further, the ligand is 1, 3-bis (diphenylphosphino) propane, and the molar ratio of the added ligand to the o-aminophenyl homopropargyl alcohol is 0.05-0.2: 1.
Further, the oxidant is copper acetate, and the molar ratio of the added oxidant to the o-aminophenyl homopropargyl alcohol is 1.0-2.0: 1, preferably 1.5-2.0: 1.
Further, the solvent is a mixed solvent of acetonitrile and toluene in a volume ratio of 1: 1.
Further, the stirring reaction time is 3-9 hours, preferably 6-9 hours.
Further, the separation and purification operations are as follows: extracting the reaction liquid with ethyl acetate for 3 times, combining organic phases, drying with anhydrous magnesium sulfate, filtering, distilling under reduced pressure to remove the organic solvent to obtain a crude product, and purifying by column chromatography to obtain the 2-aminoquinoline dihydrofuran compound.
Furthermore, the eluent for column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20-30: 1, preferably a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 25-30: 1.
The reaction principle of the synthetic method is that o-aminophenyl homopropargyl alcohol and isonitrile are used as raw materials, under the combined action of a palladium salt catalyst and an oxidant, the reaction is started through intramolecular palladium oxide oxidation, isonitrile is migrated and inserted, a generated alkyl carbon palladium bond is captured by another nucleophilic reagent amino in a molecule, and the 2-aminoquinoline dihydrofuran compound is synthesized in one step through reduction elimination.
Compared with the prior art, the invention has the following advantages and beneficial effects:
(1) the invention develops a synthetic method for constructing a 2-aminoquinoline dihydrofuran compound with unique performance by the serial cyclization reaction of o-aminophenyl homopropargyl alcohol and isonitrile, wherein the basic raw material o-aminophenyl homopropargyl alcohol can be synthesized by cheap o-iodoaniline and 3-butyn-1-ol, and the synthetic method has the characteristics of simple and easily obtained raw materials, cheap operation, mild conditions, high atom economy and wide substrate applicability;
(2) the synthetic method is novel and efficient, has good tolerance to functional groups, and is expected to be applied to actual industrial production and further derivatization.
Drawings
FIGS. 1 and 2 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 1, respectively;
FIGS. 3 and 4 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 2, respectively;
FIGS. 5 and 6 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 3, respectively;
FIGS. 7 and 8 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 4;
FIGS. 9 and 10 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 5;
FIGS. 11 and 12 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 6;
FIGS. 13 and 14 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 7;
FIGS. 15 and 16 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 8;
FIGS. 17 and 18 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 9;
FIGS. 19 and 20 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 10;
FIGS. 21 and 22 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 11;
FIGS. 23 and 24 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 12;
FIGS. 25 and 26 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 13;
fig. 27 and 28 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 14, respectively.
Detailed Description
The technical solutions of the present invention are further described in detail below with reference to specific examples and drawings, but the scope and implementation of the present invention are not limited thereto.
Example 1
To the reaction tube were added 0.2 mmol of N-4- (2-aminophenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 68%.
The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 1 and fig. 2, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.72(d,J＝8.4Hz,2H),7.48(t,J＝7.8Hz,1H),7.16(t,J＝7.6Hz,1H),4.80(t,J＝9.0Hz,2H),4.01(s,1H),3.05(t,J＝9.0Hz,2H),1.60(s,9H)；
13C NMR(101MHz,CDCl3)δ162.6,154.2,149.1,128.9,126.7,121.0,113.6,103.6,72.3,51.8,29.5,27.8；
IR(KBr)νmax 3440,3055,2957,1573,1231,1076,918,751,629,549cm-1；
HRMS(ESI)Calcd for C15H19N2O[M+H]+:243.1492,Found 243.1494.。
the structure of the target product is deduced from the above data as follows:
example 2
To the reaction tube were added 0.2 mmol of N-4- (2-amino-5-chlorophenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane, 0.4 mmol of anhydrous copper acetate and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 49%.
The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 3 and 4, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.70(d,J＝1.8Hz,1H),7.61(d,J＝8.6Hz,1H),7.08(dd,J＝8.6,1.9Hz,1H),4.79(t,J＝9.0Hz,2H),4.07(s,1H),3.03(t,J＝9.0Hz,2H),1.57(s,9H)；
13C NMR(101MHz,CDCl3)δ162.5,154.8,149.7,134.6,125.7,122.3,121.6,112.0,103.7,72.4,51.9,29.5,27.4；
IR(KBr)νmax 3437,2956,1639,1579,1510,1433,1385,1216,1078,918,741,637,537cm-1；
HRMS(ESI)Calcd for C15H18ClN2O[M+H]+:277.1102,Found:277.1104。
the structure of the target product is deduced from the above data as follows:
example 3
To a reaction tube were added 0.2 mmol of N-4- (2-amino-4-bromophenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 25:1 as eluent to obtain the target product with a yield of 58%.
The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 5 and 6, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.79(s,1H),7.45(d,J＝8.5Hz,1H),7.13(d,J＝8.6Hz,1H),4.70(t,J＝9.0Hz,2H),3.99(s,1H),2.93(t,J＝9.0Hz,2H),1.47(s,9H)；
13C NMR(101MHz,CDCl3)δ162.6,154.7,149.9,128.9,124.2,123.0,122.4,112.3,103.9,72.4,51.9,29.5,27.4；
IR(KBr)νmax 3427,2953,1634,1520,1429,1224,1145,1079,1017,915,826,749,645,454cm-1；
HRMS(ESI)Calcd for C15H18BrN2O[M+H]+:321.0597,Found 321.0600。
the structure of the target product is deduced from the above data as follows:
example 4
To the reaction tube were added 0.2 mmol of N-4- (2-amino-4-methoxyphenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane, 0.4 mmol of anhydrous copper acetate and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 61%.
The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 7 and fig. 8, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.49(d,J＝8.8Hz,1H),7.00(s,1H),6.70(d,J＝8.8Hz,1H),4.64(t,J＝8.9Hz,2H),3.80(s,3H),2.89(t,J＝8.9Hz,2H),1.48(s,9H)；
13C NMR(101MHz,CDCl3)δ162.8,160.7,154.7,150.9,122.1,112.9,108.0,106.3,101.4,72.3,55.2,51.8,29.6,27.3；
IR(KBr)νmax 3438,2950,1637,1578,1508,1433,1382,1211,1004,914,740,509cm-1；
HRMS(ESI)Calcd for C16H20N2NaO2[M+Na]+:295.1417,Found:295.1414。
the structure of the target product is deduced from the above data as follows:
example 5
To the reaction tube were added 0.2 mmol of N-4- (2-amino-4-esterylphenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 56%.
The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 9 and fig. 10, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ8.39(s,1H),7.73(d,J＝2.6Hz,1H),4.78(t,J＝9.0Hz,2H),3.94(s,1H),3.03(t,J＝9.0Hz,2H),1.57(s,9H)；
13C NMR(101MHz,CDCl3)δ167.6,162.3,154.6,130.2,129.0,121.3,120.7,116.3,105.7,72.4,52.0,51.9,29.4,27.5；
IR(KBr)νmax 3406,2949,1715,1634,1519,1424,1233,1087,989,912,746,547,461cm-1；
HRMS(ESI)Calcd for C17H21N2O3[M+H]+:301.1547,Found 301.1551.。
the structure of the target product is deduced from the above data as follows:
example 6
To the reaction tube were added 0.2 mmol of N-4- (2-amino-5-chlorophenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 74%.
The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 11 and fig. 12, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.69(d,J＝1.7Hz,1H),7.61(d,J＝8.6Hz,1H),7.08(dd,J＝8.6,1.9Hz,1H),4.80(t,J＝9.0Hz,2H),4.06(s,1H),3.04(t,J＝9.0Hz,2H),1.56(s,9H)；
13C NMR(101MHz,CDCl3)δ162.6,154.8,149.7,134.7,125.8,122.3,121.6,112.0,103.7,72.4,51.9,29.5,27.4；
IR(KBr)νmax 3439,2928,1639,1511,1436,1385,1217,1008,919,868,749,639cm-1；
HRMS(ESI)Calcd for C15H18ClN2O,[M+H]+:277.1102,Found 277.1105。
the structure of the target product is deduced from the above data as follows:
example 7
To the reaction tube were added 0.2 mmol of N-4- (2-amino-5-methylphenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 25:1 as eluent to obtain the target product with a yield of 52%.
The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 13 and fig. 14, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.61(d,J＝8.6Hz,1H),7.49(s,1H),7.41-7.04(m,1H),4.78(t,J＝9.0Hz,2H),3.94(s,1H),3.05(t,J＝8.9Hz,2H),2.43(s,3H),1.58(s,9H)；
13C NMR(101MHz,CDCl3)δ167.3,163.4,155.6,151.6,128.9,126.5,124.6,122.2,112.8,104.0,72.5,52.1,51.8,29.5,27.3；
IR(KBr)νmax 3439,2920,1637,1511,1413,1257,1080,935,818,742,549cm-1；
HRMS(ESI)Calcd for C16H21N2O[M+H]+:257.1648,Found 257.1649。
the structure of the target product is deduced from the above data as follows:
example 8
To the reaction tube were added 0.2 mmol of N-4- (2-amino-5-trifluoromethylphenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) was added to the mixture, and 0.3 mmol of t-butylisonitrile was added thereto, and the mixture was stirred at 100 ℃ and 700rpm for 9 hours, and the stirring was stopped. Adding 5mL of water, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 30:1, so that the target product is obtained, and the yield is 54%.
The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 15 and fig. 16, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ8.00(s,1H),7.74(d,J＝8.7Hz,1H),7.62(d,J＝8.7Hz,1H),4.84(t,J＝9.0Hz,2H),4.19(s,1H),3.08(t,J＝8.9Hz,2H),1.58(s,9H)；
13C NMR(100MHz,DMSO)δ152.9,128.9(q,J＝3.8Hz),126.6,126.1(d,J＝3.6Hz),123.9,116.0(q,J＝32.3Hz),113.6,106.7,95.0,77.2,60.2,29.5,24.1；
IR(KBr)νmax 3469,2925,2858,1638,1487,1172,1094,940,830,736,543cm-1；
HRMS(ESI)Calcd for C16H18F3N2O[M+H]+:311.1366,Found 311.1370。
the structure of the target product is deduced from the above data as follows:
example 9
To the reaction tube were added 0.2 mmol of N-4- (2-amino-3, 5-dimethylphenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 60%.
The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 17 and fig. 18, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.38(s,1H),7.23(s,1H),4.78(t,J＝8.9Hz,2H),3.96(s,1H),3.05(t,J＝8.9Hz,2H),2.66(s,3H),2.41(s,3H),1.62(s,9H)；
13C NMR(101MHz,CDCl3)δ162.7,152.5,146.4,134.2,131.2,129.9,117.8,112.9,103.2,72.2,51.6,29.3,27.5 21.2,18.8；
IR(KBr)νmax 3437,2960,1640,1437,1218,1112,976,851,775,623,492cm-1；
HRMS(ESI)Calcd for C17H23N2O[M+H]+:271.1805,Found 271.1808。
the structure of the target product is deduced from the above data as follows:
example 10
To the reaction tube were added 0.2 mmol of N-4- (2-amino-3, 5-dichlorophenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 66%.
The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 19 and fig. 20, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.57(dd,J＝9.0,2.3Hz,1H),4.81(t,J＝9.0Hz,2H),4.17(s,1H),3.05(t,J＝9.0Hz,2H),1.60(s,9H)；
13C NMR(101MHz,CDCl3)δ162.3,153.9,131.8,129.3,125.1,119.3,114.8,105.1,72.8,52.2,29.1,27.3；
IR(KBr)νmax 3440,2924,1641,1589,1514,1402,1259,1212,1123,948,845,742,504cm-1；
HRMS(ESI)Calcd for C15H17Cl2N2O[M+H]+:311.0712,Found 311.0716。
the structure of the target product is deduced from the above data as follows:
example 11
To the reaction tube were added 0.2 mmol of N-4- (2-aminophenyl) but-3-yn-2-ethyl-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, and finally 0.3 mmol of t-butyl isonitrile, and stirring and reacting at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 65%.
The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 21 and 22, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.83-7.65(m,1H),7.53-7.42(m,1H),7.16(t,J＝7.5Hz,1H),4.99(dq,J＝9.5,6.7Hz,1H),3.99(s,1H),3.12(dd,J＝14.2,9.5Hz,1H),2.71(dd,J＝14.2,7.3Hz,1H),2.03-1.87(m,1H),1.87-1.75(m,1H),1.61(s,3H),1.10(t,J＝7.4Hz,3H)；
13C NMR(101MHz,CDCl3)δ162.0,154.3,149.1,128.8,126.7,121.1,120.88,113.6,103.2,86.2,51.8,32.6,29.6,29.2,9.4；
IR(KBr)νmax 3429,3061,2956,1639,1516,1409,1227,996,908,756,638cm-1；
HRMS(ESI)Calcd for C17H22N2NaO[M+H]+:293.1624,Found 293.1622。
the structure of the target product is deduced from the above data as follows:
example 12
To the reaction tube were added 0.2 mmol of N-4- (2-aminophenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: a mixed solvent of toluene (1:1, v/v), and finally 0.3 mmol of cyclohexyl isonitrile, and the mixture is stirred and reacted at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times with ethyl acetate, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, evaporating the solvent under reduced pressure, and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1, so as to obtain the target product with a yield of 54%.
The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 23 and 24, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.91-7.64(m,2H),7.47(ddd,J＝8.4,7.0,1.4Hz,1H),7.20-7.05(m,1H),4.80(t,J＝9.0Hz,2H),4.17(s,1H),3.09(t,J＝9.0Hz,2H),2.14(d,J＝12.5Hz,2H),1.93-1.56(m,3H),1.58-1.38(m,2H),1.39-1.12(m,4H)；
13C NMR(101MHz,CDCl3)δ163.3,154.0,149.1,129.2,126.0,121.1,121.0,113.8,102.9,72.5,49.2,33.9,27.4,25.8,25.0；
IR(KBr)νmax 3421,2924,2853,1640,1517,1408,1258,1151,1078,995,756,645cm-1；
HRMS(ESI)Calcd for C17H21N2O[M+H]+:269.1648,Found 269.1652。
the structure of the target product is deduced from the above data as follows:
example 13
To the reaction tube were added 0.2 mmol of N-4- (2-aminophenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v), and finally 0.3 mmol of adamantyl isonitrile, and the mixture is stirred and reacted at 100 ℃ and 700rpm for 9 hours; stopping stirring, adding 5mL of water, extracting for 3 times by using ethyl acetate, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, evaporating the solvent under reduced pressure, and then carrying out column chromatography separation and purification by using a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 25:1 as eluent of the column chromatography to obtain the target product, wherein the yield is 62%.
The hydrogen spectrum and the carbon spectrum of the obtained target product are respectively shown in fig. 25 and 26, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.69(dd,J＝7.5,4.5Hz,1H),7.46(t,J＝7.4Hz,1H),7.13(t,J＝7.4Hz,1H),4.80(t,J＝9.0Hz,1H),3.90(s,1H),3.05(t,J＝8.9Hz,2H),2.28(s,6H),2.15(s,3H),1.76(q,J＝12.2Hz,6H)；
13C NMR(101MHz,CDCl3)δ162.7,154.2,149.1,128.9,126.6,121.0,113.6,103.5,72.3,52.4,42.5,36.7,29.8,27.5；
IR(KBr)νmax 3414,2904,1636,1511,1404,1264,1150,1079,992,919,743,640,541,457cm-1；
HRMS(ESI)Calcd for C21H25N2O[M+H]+:321.1961,Found 321.1968。
the structure of the target product is deduced from the above data as follows:
example 14
To the reaction tube were added 0.2 mmol of N-4- (2-aminophenyl) but-3-yn-1-ol, 0.02 mmol of tetratriphenylphosphine palladium, 0.4 mmol of anhydrous copper acetate, 0.04 mmol of 1, 3-bis (diphenylphosphino) propane and 2 ml of acetonitrile: toluene (1:1, v/v) mixed solvent, finally 0.3 mmol of 1,1,4, 4-tetramethylbutylisonitrile added, and stirred at 100 ℃ and 700rpm for reaction for 9 hours; stopping stirring, adding 5mL of water, extracting with ethyl acetate for 3 times, combining the organic phases, drying with 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as eluent to obtain the target product with a yield of 73%.
The hydrogen spectrum and the carbon spectrum of the obtained target product are respectively shown in fig. 27 and 28, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ7.72(dd,J＝8.2,2.8Hz,2H),7.48(t,J＝7.3Hz,1H),7.15(t,J＝7.4Hz,1H),4.80(t,J＝9.0Hz,2H),4.07(s,1H),3.04(t,J＝9.0Hz,2H),2.05(s,2H),1.66(s,6H),1.04(s,9H)；
13C NMR(101MHz,CDCl3)δ162.5,154.1,149.2,128.8,126.7,120.9,113.6,103.5,72.2,55.8,51.9,31.8,31.6,29.9,27.5；
IR(KBr)νmax 3691,3443,2952,1642,1518,1410,1229,1150,1077,1000,931,752,630cm-1；
HRMS(ESI)Calcd for C19H27N2O[M+H]+:299.2118,Found 299.2122。
the structure of the target product is deduced from the above data as follows:
the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (8)
1. A synthetic method of 2-aminoquinoline dihydrofuran compounds is characterized by comprising the following steps:
dissolving o-aminophenyl homopropargyl alcohol, a palladium salt catalyst, a ligand and an oxidant in an organic solvent in a reactor, adding isonitrile, stirring for reaction at 80-100 ℃, and separating and purifying reaction liquid to obtain the 2-aminoquinoline dihydrofuran compound;
the chemical reaction equation of the synthesis process is as follows:
in the formula, R1Is a substituent on the benzene ring, R1More than one selected from 4-methyl, 4-bromine, 4-methoxyl, 4-ester group, 5-chlorine, 5-methyl, 5-trifluoromethyl, 5-bromine, 6-fluorine, 3, 5-dimethyl, 3, 5-dichloro, 4, 6-dimethyl and 4, 6-dichloro;
R2selected from hydrogen or ethyl;
R3selected from tert-butyl, cyclohexyl, adamantyl or 1,1,4, 4-tetramethylbutyl; the palladium salt catalyst is palladium tetratriphenylphosphine; the ligand is 1, 3-bis (diphenylphosphino) propane; the oxidant is copper acetate.
2. The synthesis method according to claim 1, wherein the molar ratio of the added palladium salt catalyst to the o-aminophenyl homopropargyl alcohol is 0.05-0.1: 1.
3. The method of claim 1, wherein the molar ratio of the ligand to the o-aminophenylhomopropargyl alcohol is 0.05 to 0.2: 1.
4. The synthesis method according to claim 1, wherein the molar ratio of the added oxidant to the o-aminophenylhomopropargyl alcohol is 1.5-2.0: 1.
5. The synthesis method according to claim 1, wherein the organic solvent is a mixed solvent of acetonitrile and toluene in a volume ratio of 1: 1.
6. The synthesis method according to claim 1, wherein the stirring reaction time is 6 to 9 hours.
7. The synthesis method according to claim 1, characterized in that the separation and purification operations are: extracting the reaction liquid with ethyl acetate for 3 times, combining organic phases, drying with anhydrous magnesium sulfate, filtering, distilling under reduced pressure to remove the organic solvent to obtain a crude product, and purifying by column chromatography to obtain the 2-aminoquinoline dihydrofuran compound.
8. The synthesis method of claim 7, wherein the eluent for the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 25-30: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810171226.6A CN108409747B (en) | 2018-02-28 | 2018-02-28 | Synthetic method of 2-aminoquinoline dihydrofuran compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810171226.6A CN108409747B (en) | 2018-02-28 | 2018-02-28 | Synthetic method of 2-aminoquinoline dihydrofuran compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108409747A CN108409747A (en) | 2018-08-17 |
| CN108409747B true CN108409747B (en) | 2021-09-21 |
Family
ID=63129669
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810171226.6A Active CN108409747B (en) | 2018-02-28 | 2018-02-28 | Synthetic method of 2-aminoquinoline dihydrofuran compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108409747B (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108993600B (en) * | 2018-08-30 | 2021-01-22 | 郑州大学 | Use of bidentate phosphite ligands in C-B bond building reactions |
| CN111303096B (en) * | 2020-03-24 | 2021-12-28 | 海南医学院 | Synthesis method of polysubstituted 1, 3-dihydronaphtho [2,3-c ] furan derivative |
| CN111592509B (en) * | 2020-06-08 | 2022-11-22 | 江苏师范大学 | Method for synthesizing aryl (3-sulfuryl benzofuran-2-yl) ketone compound by copper catalysis |
| CN111732592A (en) * | 2020-07-02 | 2020-10-02 | 湖北文理学院 | Condensed ring compound containing indole skeleton and preparation method thereof |
| CN111732546A (en) * | 2020-07-02 | 2020-10-02 | 湖北文理学院 | Fused ring compound containing imidazole skeleton and preparation method thereof |
| CN112592352A (en) * | 2020-12-23 | 2021-04-02 | 华南理工大学 | Polysubstituted benzothienopyridine compound and preparation method thereof |
| CN112679521B (en) * | 2020-12-28 | 2021-12-14 | 江西理工大学 | Method for synthesizing mild azaspiro tricyclic framework molecule |
| CN114560838B (en) * | 2022-03-18 | 2023-09-15 | 遵义医科大学 | Preparation method of 2-amino-3-formyl chromone compound |
| CN115626904A (en) * | 2022-11-09 | 2023-01-20 | 华南理工大学 | 3-enamide substituted benzodihydrofuran compound and preparation method thereof |
| CN115785102A (en) * | 2022-11-24 | 2023-03-14 | 华南理工大学 | Synthetic method of iodo-indole quinazoline amine compound |
| CN116640149A (en) * | 2023-05-29 | 2023-08-25 | 上海大学 | Quinoline fused ring compound and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140235855A1 (en) * | 2011-06-17 | 2014-08-21 | Berangere Gaucher | Tricyclic Antibiotics |
| CN105541837A (en) * | 2016-01-29 | 2016-05-04 | 安徽理工大学 | Preparation method of 1-arylimidazo[1,5-a]quinoline compounds |
-
2018
- 2018-02-28 CN CN201810171226.6A patent/CN108409747B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140235855A1 (en) * | 2011-06-17 | 2014-08-21 | Berangere Gaucher | Tricyclic Antibiotics |
| CN105541837A (en) * | 2016-01-29 | 2016-05-04 | 安徽理工大学 | Preparation method of 1-arylimidazo[1,5-a]quinoline compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108409747A (en) | 2018-08-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108409747B (en) | Synthetic method of 2-aminoquinoline dihydrofuran compound | |
| CN108299423B (en) | Synthesis method of dihydropyrrolo-2-aminoquinoline compound | |
| Tsubokura et al. | Direct guanylation of amino groups by cyanamide in water: catalytic generation and activation of unsubstituted carbodiimide by scandium (III) triflate | |
| Tang et al. | Synthesis of a water-soluble cationic chiral diamine ligand bearing a diguanidinium and application in asymmetric transfer hydrogenation | |
| CN112592352A (en) | Polysubstituted benzothienopyridine compound and preparation method thereof | |
| CN109810147B (en) | Pyrene-labeled benzimidazole nitrogen heterocyclic carbene palladium metal complex, and preparation and application thereof | |
| CN108864164B (en) | Synthesis method of primary amine-guided 2-alkynyl indole compound | |
| CN112920072B (en) | NOBIN biaryl compound and synthetic method thereof | |
| CN114989063A (en) | Synthesis method of beta-halopyrrole compound | |
| CN106316871B (en) | A kind of amino acid derivativges of chiral beta 2 and preparation method thereof | |
| Singh et al. | Cationic ruthenium (II)-CNC pincer complexes as phosphine-free catalysts for nitrile hydration to amides in aqueous medium | |
| CN114874126A (en) | Synthetic method of 3-bromoindole compound | |
| CN112778351A (en) | Preparation method of beta-dimethylphenyl silicon substituted aromatic nitro compound | |
| CN109867694B (en) | Synthesis method of oxygen-guided 7-alkynyl indole compound | |
| CN113444040A (en) | Method for synthesizing chiral alpha-unnatural amino acid derivative under drive of visible light | |
| CN109761875B (en) | Novel method for constructing amido bond | |
| CN109748809B (en) | Method for synthesizing 2-substituted amino-1, 4-naphthoquinone derivative | |
| CN113024611A (en) | Novel N-heterocyclic carbene cyclic palladium compound and preparation method and application thereof | |
| CN112480004A (en) | 5-trifluoromethyl substituted pyrazole derivative and synthesis method and application thereof | |
| CN111646889B (en) | Green synthesis method of drug active molecules GC-24 and furaldehyde | |
| WO2023151188A1 (en) | Green synthesis method of antiviral drug intermediate | |
| CN112679431B (en) | Method for preparing isoquinolinones compound | |
| CN112645984B (en) | Half-sandwich ruthenium complex containing phenyl benzoxazole structure and preparation method and application thereof | |
| CN113200884B (en) | Chiral carboxylic acid compound and synthesis method and application thereof | |
| CN103130702A (en) | Method for synthesizing 3-substituted indole and 2,3-disubstituted indole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |